Prevención de la preeclampsia: desde la dieta hasta la aspirina: revisión de la literatura / Prevention of preeclampsia: from diet to aspirin: review of the literature

Introducción y objetivo: Explorar las estrategias de prevención de la preeclampsia que se han propuesto a lo largo de la historia. Método: Revisión narrativa de la literatura sobre la evidencia científica histórica disponible entre 2016 y 2023 acerca de la aspirina y otras estrategias de prevención de la preeclampsia, en bases de datos bibliográficas computarizadas de estudios publicados en revistas indexadas. Resultados: Varios estudios confirman la efectividad de la aspirina para prevenir la preeclampsia en población de alto riesgo, siendo un medicamento con bajo riesgo de complicaciones, con mayor evidencia de efectividad si se inicia antes de las 16 semanas de gestación y con un aparente efecto dependiente de la dosis. Intervenciones como la disminución del consumo de sal, el reposo en cama, la suplementación con ácidos grasos, antioxidantes, L-arginina, zinc o magnesio, y el uso de diuréticos o de inhibidores de la bomba de protones, no han mostrado su utilidad en la prevención de la preeclampsia. Conclusiones: La aspirina a dosis baja es un medicamento seguro en el embarazo y efectivo para prevenir la preeclampsia en población de alto riesgo. Es la estrategia de prevención más ampliamente estudiada a lo largo de la historia para la disfunción endotelial durante la gestación.

Introduction and objective: To explore the different prevention strategies for preeclampsia that have been proposed throughout the history. Method: A narrative review of the historical, scientific evidence available between 2016 and 2021 on aspirin and other preeclampsia prevention strategies in computerized bibliographic databases of studies published in indexed journals. Results: Several studies confirm the effectiveness of aspirin to prevent preterm preeclampsia in high-risk populations, considering this as a safe drug with low risk of complications, with greater evidence of effectiveness when started before 16 weeks of gestation and apparently with a dose-dependent effect. Interventions such as reducing salt intake, bed rest, supplementation with fatty acids, antioxidants, L-arginine, zinc, magnesium, the use of diuretics or proton pump inhibitors have not shown its usefulness in the prevention of high risk preeclampsia patients. Conclusions: Low-dose aspirin is a safe drug in pregnancy and is effective to prevent preeclampsia in high-risk populations. Is the most widely studied throughout history prevention strategy for endothelial dysfunction during pregnancy.

Analysis of Aspirin-related Medication Errors in the Elderly of China / 医药导报

Objective To investigate the incidence and causes of medication errors(MEs)related to aspirin in the eld-erly(≥60 years old)of China,to provide data for targeted precautions,and to promote medication safety in the elderly.Methods Reports about aspirin-related MEs in the elderly were extracted from the National Monitoring Network for Clinical Safe Drug Medication from September 22,2012 to September 22,2022.The severity of errors,content of errors,where errors were made,the personnel who made these errors,and causes of errors were analyzed retrospectively and statistically.Results A total of 386 MEs reports were extracted,235 males and 151 females,with a median age of 70(60-98)years old.Regarding the severity of MEs,errors of class B were dominating(314 cases,81.35%).As for the severe MEs(9 cases,2.33%),5 cases of ME were as-sociated with bleeding.There are four patients suffering from gastrointestinal bleeding:one patient took aspirin three times a day,one patient broke off enteric-coated tablets,one patient took aspirin as acarbose mistakenly,one patient took aspirin with Xuesai-tong for long time.One patient had urinary urgency,but did not seek medical attention in time,then developed into visible hema-turia.Two patients missed taking aspirin led to stent thrombosis.One patient suffered from diarrhea after overdosing on 29 pills of aspirin by mistake.One patient with hyperuricemia had gout after taking aspirin.Among these 386 MEs,224(58.03%)cases were triggered by physicians,the first three error factors were frequency(multiple times a day),dosage(the dosage of enteric-coated tablets is not the whole tablet),and variety.Most of these MEs were due to a lack of knowledge or training,and fatigue.Regarding the MEs caused by pharmacists(87 cases,22.54%).Pharmacists identified 274 cases(70.98%)of errors.Conclusion When it comes to aspirin-related MEs,it ought to be noticed that the drug usage and dosage,drug interaction,and selection of drug varieties when combining with other diseases(such as atrial fibrillation and hyperuricemia).It is recommended that information construction be fortified to decrease the ME of the prescription link,and the clinicians be better informed of rational drug use.At the same time,patient medication education should be improved.

Aspirin for thromboprophylaxis in orthopedic surgery: advancements in clinical evidence and guidelines / 中华创伤骨科杂志

As patients undergoing orthopedic surgery are a high-risk group for venous thromboembolism (VTE), clinical guidelines suggest anticoagulant drugs for VTE prophylaxis during perioperative period. Global antithrombotic guidelines vary in recommendations for anticoagulant drugs, but there is a general consensus in favor of using low-molecular-weight heparin (LMWH) as the first choice for prophylaxis, followed by unfractionated heparin, fondaparinux, warfarin, aspirin, and other direct oral anticoagulants (DOACs). Of them, aspirin is an inexpensive, widely used antiplatelet drug with limited complications and clear efficacy in prevention of myocardial infarction, stroke, and certain specific cancers. It was also used early for venous thromboembolism prophylaxis in orthopedic patients after surgery. Clinical experience of orthopedic physicians in North America has shown the effectiveness of aspirin in VTE prevention over several decades so that aspirin continues to be used to this day, but its use for VTE prophylaxis is less common in Europe and Asia. Historically, the role and efficacy of aspirin in VTE prevention have been the subjects of considerable controversy, for the early and recent research findings contradict each other, and recommendations conflict in different guidelines. This review focuses on the advancements in clinical evidence and guideline recommendations regarding the use of aspirin for VTE prophylaxis in major orthopedic surgeries.

Randomized clinical trial of aspirin as prophylaxis for thromboembolism in hip arthroplasty / Ensaio randomizado da aspirina na profilaxia do tromboembolismo em artroplastia do quadril

ABSTRACT Objective: This study aims to evaluate aspirin as a chemical prophylaxis (200 mg) in total hip arthroplasty. Methods: the study compared two groups and used ultrasonography (USG) to screen for low-deep venous thrombosis. Group 1 received 600 mg (control), and Group 2 received 200 mg of (intervention), associated with the use of elastic compression stockings and early walking Results: fourteen patients were allocated to Group A (200mg), and 16 to Group B (600mg); in group A (200mg), 3 cases with thrombus below the popliteal vein were detected at the first USG examination. All of them are in the left lower limb (21.4%). In group B (600 mg), 5 cases were identified after the first exam (31.2%). All cases were asymptomatic and followed the protocol with prophylaxis only with Aspirin. Conclusion: In the statistical data, there were no differences in the presence of thrombus between the 200- and 600 mg groups, which is credited to using low-dose aspirin in low doses (200mg). Hematimetric levels returned to baseline levels and suggested there was no chronic or acute bleeding related to the use of aspirin. The manuscript was prepared according to the CONSORT guideline 2010. Level of Evidence I; Longitudinal Randomized Comparative Clinical Study.

RESUMO Objetivo: Este estudo pretende avaliar a aspirina como profilaxia química (200 mg) na artroplastia total do quadril. Métodos: estudo comparando dois grupos com diferentes doses de aspirina e utilizando a ultrassonografia (USG) para rastreamento da trombose venosa profunda baixa. O grupo 1, 650 mg ao dia de aspirina (controle) e o grupo 2, 200 mg de aspirina ao dia na mesma posologia (intervenção) e associados ao uso de meias elásticas de compressão e deambulação precoce. Resultados: quatorze pacientes foram alocados no grupo A (200 mg) e 16 no grupo B (650 mg). No grupo A foram detectados 3 casos com trombos abaixo da veia poplítea ao USG sendo 21,4%. Já no grupo B, 5 casos foram identificados após o primeiro exame (31,2%). Todos assintomáticos e sem sinais de sangramento ativo ou queda da hematimetria no momento da detecção dos trombos. Conclusão: os dados sugerem não haver diferença na incidência de trombo em ambos os grupos, não sendo a profilaxia com a aspirina dose-dependente. Os níveis hematimétricos retornaram aos níveis iniciais o que sugere não ter havido sangramento crônico ou agudo relacionado ao uso. Nível de Evidência I; Estudo Clínico Randomizado Longitudinal Comparativo.

How can we reduce maternal mortality due to preeclampsia? The 4P rule

Abstract In low and middle-income countries such as Brazil, most maternal deaths are related to hypertensive complications. Preeclampsia is the leading cause of maternal mortality and morbidity. Significant proportion is associated with the following factors: lack of identification of high-risk women, lack of adequate prevention, difficulty in maintaining a high-risk prenatal follow-up, delayed diagnosis, insecurity and low use of magnesium sulphate, delayed pregnancy interruption and lack of postpartum follow-up of these high-risk cases. Four major actions are proposed to minimize this alarming clinical picture and reduce the mortality rates due to preeclampsia, called the "4 P Rule" (Adequate Prevention - Vigilant Prenatal Care - Timely Delivery (Parturition) - Safe Postpartum). From this simple "rule" we can open a range of important processes and reminders that may help in the guidance of preeclampsia management.

Aspirin in the prevention of cardiovascular disease: a review / 预防医学

Abstract@#Aspirin (ASA) is widely used for primary and secondary prevention of cardiovascular disease (CVD), but its strategy of application is highly controversial. Meanwhile, in terms of ASA prevention strategies for CVD, countries around the world are different. The United States is becoming increasingly cautious, while the European Union tends to focus on the benefits of ASA clinical use. China is concerned about the effectiveness of ASA in preventing CVD in the elderly. This article reviews relevant literature published domestically and internationally from 2005 to 2024 for the application of ASA in CVD prevention, ASA prevention strategies for CVD in main countries and the application of ASA in special groups such as chronic disease patients, which provides a basis for improving ASA prevention strategies for CVD and standardizing clinical application of ASA in China.

Meta-analysis of efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery / 中国药房

OBJECTIVE To evaluate the clinical efficacy and safety of aspirin versus other anticoagulants in the prevention of thromboembolism after orthopedic surgery. METHODS Retrieved from PubMed， Embase， the Cochrane Library， CNKI， Wanfang data and VIP， randomized controlled trials （RCTs） and cohort studies about aspirin （trial group） versus other anticoagulants （control group） were collected during the inception and June 1st， 2023. After literature screening， data extraction and quality evaluation， the meta-analysis was conducted by using RevMan 5.4 software. RESULTS A total of 22 studies were included， involving 9 RCTs and 13 cohort studies. RCT results showed that the incidences of deep vein thrombosis （DVT） [RR＝1.81， 95%CI（1.36， 2.40）， P＜0.000 1] and postoperative pulmonary embolism （PE） [RR＝1.55， 95%CI（1.01， 2.40）， P＝0.05] in trial group were significantly higher than control group. There was no statistically significant difference in the incidences of postoperative massive bleeding， postoperative surgical site infection， all-cause death， or any bleeding after surgery between 2 groups. In the cohort study， the incidence of any bleeding in trial group was significantly lower than control group [RR＝0.71，95%CI （0.64， 0.79）， P＜0.000 1]， while the differences in other indicators were not statistically significant （P＞0.05）. The results of subgroup analysis based on different anticoagulants showed that in RCT， the incidences of DVT and PE after surgery in patients using low-molecular-weight heparin （LMWH） were significantly lower than using aspirin （P＜0.05）； in the cohort study， the incidences of DVT and PE after surgery were significantly lower in patients using direct oral anticoagulants （DOAC） than using aspirin （P＜0.05）. There was no statistically significant difference in the incidence of major bleeding between patients using aspirin and using DOAC and LWMH （P＞0.05） in both RCT and cohort study. CONCLUSIONS Aspirin is equally safe as other anticoagulants for the prevention of thromboembolism after orthopedic surgery， but its efficacy may not be as good as other anticoagulants. After orthopedic surgery， other anticoagulants should be preferred to prevent venous thromboembolism， and aspirin should be carefully considered.

Correlation between long-term use of aspirin and Helicobacter pylori infection in elderly people and its effectiveness on Helicobacter pylori eradication / 中华老年医学杂志

Objective:To investigate the correlation between long-term use of low-dose aspirin and Helicobacter pylori(HP)infection in elderly people and its effectiveness on HP eradication and recurrence.Methods:A retrospective analysis was conducted on 2 834 elderly people aged 60 and above who underwent the C 13-or C 14-urea breath test(UBT)for the first time in the Physical Examination Center of the First Hospital of Lanzhou University between March 2010 and December 2019.According to the results of UBT, people were divided into an HP infection group with 1 510 patients and a non-HP infection group with 1 324 patients.Univariate and multivariate Logistic regression analysis were used to investigate the relationship between aspirin use and HP infection.Additionally, in a prospective case-control analysis, 544 elderly hypertensive patients diagnosed with HP infection between March 2015 and December 2020 were selected and divided into an aspirin group(402 cases)and an observation group(142 cases), based on whether aspirin was used.The aspirin group was further divided into a 1 to <2 years group(134 cases), a ≥2 to <5 years group(142 cases)and a ≥5 years group(126 cases)based on the duration of aspirin treatment.The rates of HP eradication, safety and one-year post-treatment HP recurrence with bismuth-containing quadruple therapy were compared. Results:The overall HP infection rate was 53.28%(1 510/2 834).Univariate analysis showed that the infection rate in women was higher than in men[56.86%(584/1 027) vs.51.25%(926/1 807), χ2=8.307, P=0.004].The infection rate in aspirin users was higher than in non-aspirin users[57.29%(920/1 606) vs.48.05%(590/1 228), χ2=23.866, P<0.001], with no significant difference between aspirin use for 1-<2 years, ≥2-<5 years and ≥5 years[60.22%(162/269) vs.56.4%(273/484) vs.56.86%(485/853), χ2=1.166, P=0.558].Fasting blood glucose levels in the HP infection group were higher than in the non-HP infection group[(5.92±1.78)mmol/L vs.(5.77±1.40)mmol/L, t=2.317, P=0.021].Multivariate Logistic regression analysis showed the risk of HP infection in women was higher than in men( OR=1.254, 95% CI: 1.075-1.464, P=0.004).Long-term aspirin use increased the risk of HP infection( OR=1.450, 95% CI: 1.249-1.684, P<0.001).Among the 544 cases selected for eradication therapy, 522 completed the treatment protocol, with 479 achieving successful eradication.The overall eradication rate was 91.76%(479/522)according to per-protocol(PP)analysis and 88.05%(479/544)according to intention-to-treat(ITT).After 1 year, 472 cases underwent reexamination, with an overall recurrence rate of 3.6%(17/472).There was no statistical significance in the eradication rate and recurrence rate among the groups with different durations of aspirin treatment and the observation group. Conclusions:Long-term use of low-dose aspirin increases the risk of HP infection in the elderly, but does not affect the eradication rate and one-year recurrence rate of bismuth-containing quadruple therapy.Therefore, periodic screening and eradication of HP should be performed.

The Role and Mechanism of Aspirin Combined with Rehabilitation Training in the Repair of Sciatic Nerve Injury and the Changes in the Schwannocytus (Schwann Cells) in Rats / Rol y Mecanismo de la Aspirina Combinados con Entrenamiento de Rehabilitación en la Reparación de la Lesión del Nervio Ciático y los Cambios en los Schwannocitos (Células de Schwann) en Ratas

SUMMARY: This study investigated the role and mechanism of aspirin combined with rehabilitation training in the nerve injury repair and Schwann cell changes in rats with sciatic nerve injury. Totally, 120 male healthy SD rats were randomly divided into sham, model, aspirin, and aspirin + rehabilitation groups, with 30 rats in each group. The sciatic nerve function index (SFI), photothermal pain tolerance threshold and inclined plane test results at 4, 6, and 8 weeks after operation were compared. The distance of sensory nerve regeneration and the expression of S100B protein in Schwann cells were analyzed. Compared with the sham group, the SFI of the model, aspirin, and aspirin+rehabilitation groups were significantly lower at 4, 6, and 8 weeks after operation. However, the aspirin and aspirin+rehabilitation groups had significantly higher SFI than the model group. The SFI at 6 and 8 weeks after operation was higher in the aspirin+rehabilitation group than that in the aspirin group (P<0.05). The photothermal pain tolerance threshold of the sham, aspirin, and aspirin+rehabilitation groups were significantly higher than those of the model group at 4, 6, and 8 weeks after operation (P<0.05). The inclination angles of the model, aspirin, and aspirin+rehabilitation groups were significantly lower than those of the sham group at 4, 6, and 8 weeks after operation, and the inclination angle of the aspirin+rehabilitation group was significantly higher than that of the model and aspirin groups (P<0.05). The sensory nerve regeneration distance in aspirin and aspirin+rehabilitation groups was higher than that in the sham and model groups (P<0.05). The expression of S100B protein in the aspirin and aspirin+rehabilitation groups was higher than that in the model group (P<0.05). Aspirin combined with rehabilitation training can promote the functional recovery of sciatic nerve injury, and the mechanism may be related to the increase of the expression of S100B protein in Schwann cells.

En este estudio se investigó el papel y el mecanismo que desempeña la aspirina combinada, con el entrenamiento de rehabilitación en la reparación de lesiones nerviosas y los cambios en los schwannocitos en ratas con lesiones en el nervio ciático. En total, 120 ratas SD macho sanas se dividieron aleatoriamente en cuatro grupos de 30 ratas en cada uno: simulación, modelo, aspirina y aspirina + rehabilitación. Se compararon el índice de función del nervio ciático (SFI), el umbral de tolerancia al dolor fototérmico y los resultados de la prueba del plano inclinado a las 4, 6 y 8 semanas después de la operación. Se analizó la distancia de regeneración del nervio sensorial y la expresión de la proteína S100B en los schwannocitos. En comparación con el grupo simulado, el SFI de los grupos modelo, aspirina y aspirina+rehabilitación fue significativamente menor a las 4, 6 y 8 semanas después de la operación. Sin embargo, los grupos de aspirina y aspirina + rehabilitación tuvieron un SFI significativamente más alto que el grupo modelo. El SFI a las 6 y 8 semanas después de la operación fue mayor en el grupo de aspirina + rehabilitación que en el grupo de aspirina (P<0,05). El umbral de tolerancia al dolor fototérmico de los grupos simulado, aspirina y aspirina+rehabilitación fue significativamente mayor que el del grupo modelo a las 4, 6 y 8 semanas después de la operación (P<0,05). Los ángulos de inclinación de los grupos modelo, aspirina y aspirina+rehabilitación fueron significativamente menores que los del grupo simulado a las 4, 6 y 8 semanas después de la operación, y el ángulo de inclinación del grupo aspirina+rehabilitación fue significativamente mayor que el de los grupos modelo y aspirina (P<0.05). La distancia de regeneración del nervio sensorial en los grupos de aspirina y aspirina+rehabilitación fue mayor que en los grupos simulado y modelo (P<0,05). La expresión de la proteína S100B en los grupos de aspirina y aspirina+rehabilitación fue mayor que en el grupo modelo (P<0,05). La aspirina combinada con el entrenamiento de rehabilitación puede promover la recuperación funcional de la lesión del nervio ciático, y el mecanismo puede estar relacionado con el aumento de la expresión de la proteína S100B en los schwannocitos.

Uso de aspirina en prevención primaria cardiovascular: es tiempo de cambiar el paradigma / Aspirin use for primary cardiovascular prevention: time for a paradigm shift

La Aspirina es una droga ampliamente utilizada con un protagonismo indiscutido en el escenario de la prevención secundaria. Sin embargo, el rol de este medicamento en prevención primaria es aún motivo de discusión. Los primeros ensayos que evaluaron la Aspirina en prevención primaria sugerían reducciones en el infarto agudo al miocardio y el accidente cerebrovascular -aunque no en la mortalidad- con un riesgo no despreciable de hemorragia mayor. Esto llevó a diversas sociedades científicas a recomendar su prescripción sólo en aquellos individuos con alto riesgo de eventos cardiovasculares. Desde el año 2018 en adelante, surgen diversos ensayos aleatorizados que han cuestionado estas indicaciones, mostrando beneficios clínicos muy discretos o ausentes. El objetivo de esta revisión es realizar un análisis histórico de la evidencia sobre el rol de la Aspirina en prevención primaria y resumir las recomendaciones actuales en este escenario.

Aspirin is widely used with a clear role in secondary prevention of cardiovascular diseases. However, its benefit in primary prevention is still a matter of discussion. The first trials evaluating Aspirin for primary prevention suggested reductions in acute myocardial infarction and stroke (although not in mortality) but with a non-negligible risk of major bleeding. This led to aspirin being recommended by various scientific societies, albeit limited to individuals at high risk of cardiovascular events. Since 2018 various randomized trials in primary prevention showed minimal or no beneficial effects of aspirin thus questioning its indication for this purpose. The aim of this review is to make an historical analysis of the evidence for the role of Aspirin in primary prevention and suggest modified recommendations for these subjects.

Low Dose Aspirin for Primary Prevention of Adverse Pregnancy Outcome

Background: Pregnancy is associated with various complications such as pre-eclampsia, SGA, preterm birth etc. Low dose aspirin is a possible medication to minimize these adverse outcomes. The aim of this study was to evaluate the use of low dose aspirin for primary prevention of adverse pregnancy outcome. Material & Methods: This cross-sectional study was conducted in department of Gynaecology, North Bengal Medical College Hospital, Mirjapur Bkash Hospital, Mirjapur, Tangail, Bangladesh, during the period from June 2021 to August 2022. Total 200 pregnant women were included in this study. Results: In this study, the mean (±SD) age of the study subjects were 25.12 ± 5.49 years and 25.00 ± 4.83 years in LDA group and control group, respectively. There was no statistically significant (p>0.05) difference in age between the groups. The rate of caesarean section was higher in control group (68%) compared to LDA group (59%) but there was no statistically significant (p>0.05) difference among the groups. In our study, 8% pregnant women in LDA group and 19% pregnant women in control group had gestational hypertension, pre-eclampsia was seen in 6% and 13% pregnant women in LDA group and control group, respectively, preterm birth was seen in 8% and 17% pregnant women in LDA group and control group, respectively, SGA was seen in 19% and 32% pregnant women in LDA group and control group, respectively, and fetal distress was seen in 2% pregnant women in both LDA group and control group. There were statistically significant (p<0.05) differences in complications except fetal distress. Mean (±SD) neonatal birth weight was 2.88±1.03 kg and 2.74±0.85 kg in LDA group and control group, respectively and there was no statistically significant (p>0.05) difference. Conclusion: We found that low dose aspirin could significantly reduce the risk of adverse outcomes, especially for pre-eclampsia, SGA and preterm birth.

Impact of pharmacogenetics on aspirin resistance: a systematic review / Impacto da farmacogenética na resistência à aspirina: uma revisão sistemática

Abstract Background Pharmacogenetics promises better control of diseases such as cardiovascular disease (CVD). Acetylsalicylic acid, aspirin, prevents the formation of an activating agent of platelet aggregation and vasoconstriction, and it is used to prevent CVD. Nevertheless, patients may have treatment failure due to genetic variants that modify the metabolism of the drug causing aspirin resistance (AR). Objectives To realize a systematic literature review to determine the impact of genetic variants on AR. Methods Articles published in the MEDLINE/PubMed, Cochrane, Scopus, LILACS, and SCIELO databases were systematically screened. A total of 290 articles were identified and 269 articles were excluded because they did not comply with the previously established inclusion criteria. A total of 20 case-control studies and 1 cohort was included. Results The genetic variants rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2), and rs5918 (ITGB3) were the most studied. As for relevance, of the 64 genetic variants evaluated by the articles, 14 had statistical significance (p< 0.05; 95% confidence interval [CI]) in at least one article. Among them, the following have had unanimous results: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 and rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 and rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP), and rs662 (PON1), while these differ in real interference in AR: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1), and rs20417 (PTGS2). As study limitations, we highlight the nonuniform methodologies of the analyzed articles and population differences. Conclusion It is noteworthy that pharmacogenetics is an expanding area. Therefore, further studies are needed to better understand the association between genetic variants and AR.

Resumo Antecedentes A farmacogenética promete melhorar o controle de doenças como as cardiovasculares. O ácido acetilsalicílico, a aspirina, previne a formação de um agente ativador da agregação plaquetária e vasoconstrição e é usado na prevenção de tais doenças. No entanto, os pacientes podem ter falha no tratamento devido a variantes genéticas que modificam o metabolismo da droga causando resistência à aspirina (RA). Objetivos Realizar uma revisão sistemática da literatura para determinar o impacto das variantes genéticas na resistência à aspirina. Métodos Artigos publicados nos bancos de dados MEDLINE/PubMed, Cochrane, Scopus, LILACS e SCIELO foram sistematicamente selecionados. Foram identificados 290 artigos e, destes, 269 artigos foram excluídos por não atenderem aos critérios de inclusão previamente estabelecidos. Um total de 20 estudos caso-controles e 1 coorte foi incluído. Resultados As variantes genéticas rs1126643 (ITGA2), rs3842787 (PTGS1), rs20417 (PTGS2) e rs5918 (ITGB3) foram as mais estudadas. Quanto à relevância, das 64 variantes genéticas avaliadas pelos artigos, 14 tiveram significância estatística (p< 0,05; intervalo de confiança [IC] de 95%) em pelo menos um artigo. Entre eles, os seguintes tiveram resultados unânimes: rs1371097 (P2RY1), rs1045642 (MDR1), rs1051931 e rs7756935 (PLA2G7), rs2071746 (HO1), rs1131882 e rs4523 (TBXA2R), rs434473 (ALOX12), rs9315042 (ALOX5AP) e rs662 (PON1), enquanto estes diferiram na interferência real na RA: rs5918 (ITGB3), rs2243093 (GP1BA), rs1330344 (PTGS1) e rs20417 (PTGS2). Como limitações do estudo, destacam-se as metodologias não uniformes dos artigos analisados e as diferenças populacionais. Conclusão Vale ressaltar que a farmacogenética é uma área em expansão. Portanto, mais estudos são necessários para entender melhor a associação entre variantes genéticas e RA.

Effects of aspirin-induced GSDME-dependent pyroptosis on the proliferation of colorectal cancer cells / 安徽医科大学学报

Objective To investigate the effect of aspirin-induced Gasdermin E(GSDME)dependent pyroptosis and the related mechanism of colorectal cancer cell proliferation.Methods The colorectal cancer cells Caco2 were cultured in vitro.MTT assay was used to detect the effects of aspirin intervention with different concentrations(1.0,2.5,5.0,10.0,15.0,20.0 mmol/L)on the proliferation activity of colorectal cancer cells.The effect of aspirin intervention on the morphology of colorectal cancer cells was observed under the microscope.Lactate dehy-drogenase(LDH)release assay was used to investigate the effect of aspirin intervention on cell membrane integrity.The protein expression levels of NOD-like receptor protein(NLRP3),cysteinyl aspartate and specific proteinase 1(Caspase-1),Gasdermin E-N(GSDME-N)in colorectal cancer cells were detected by Western blot.The contents of interleukin-1 β(IL-1 β)and interleukin-18(IL-18)in cell supernatant after GSDME silencing were detected by ELISA.After silencing GSDME,cell morphological changes were observed under a microscope,and cell membrane integrity was observed by LDH release assay;The contents of IL-1 β and IL-18 in cell supernatant were determined by ELISA after GSDME silencing.Results MTT results showed that aspirin could decrease the proliferation activi-ty of Caco-2 in a concentration-dependent manner(P＜0.01).Morphological observation and LDH experiment showed that aspirin could promote the occurrence of pyroptosis(P＜0.05).Western blot showed that aspirin could increase the expression levels of NLRP3,Caspase-1,GSDME-N of pyroptosis-related pathway genes(P＜0.05).ELISA showed that aspirin could significantly increase the concentration of IL-1 β and IL-18 in Caco-2 cells(P＜0.01).After GSDME silencing,the pyroptosis was significantly inhibited(P＜0.05)and the expression of IL-1 βand IL-18 decreased significantly(P＜0.01).Conclusion Aspirin can inhibit the proliferation of Caco-2 by indu-cing the pyroptosis of GSDME-dependent cells,thus inhibiting colon cancer.

High on-treatment platelet reactivity in patients with ischemic stroke or transient ischemic attack / 国际脑血管病杂志

Antiplatelet drugs are the cornerstone of long-term treatment and secondary prevention for ischemic stroke/transient ischemic attack (TIA) recommended by guidelines, aimed at reducing the risk of recurrent stroke and other cardiovascular events. However, some patients with ischemic stroke/TIA may still experience ischemic events during antiplatelet therapy, known as high on-treatment platelet reactivity (HTPR), which typically occurs in patients taking aspirin or clopidogrel. This article elaborates the incidence, risk factors, and commonly used evaluation methods of HTPR in patients with ischemic stroke/TIA, and elucidates the clinical significance of HTPR in patients with ischemic stroke/TIA, and investigates the antiplatelet treatment protocol of patients with HTPR.

Correlation between adverse events and antiplatelet drug resistance after neurovascular intervention for cerebrovascular stenosis / 中国基层医药

Objective:To investigate the correlation between adverse events and antiplatelet drug resistance after neurovascular intervention for cerebrovascular stenosis.Methods:A total of 148 patients with cerebrovascular stenosis who underwent neurovascular intervention at Wenzhou Hospital of Integrated Traditional Chinese and Western Medicine from January 2020 to December 2020 were included in this study. The platelet function of patients before and 24 hours after antiplatelet drug treatment was recorded. Platelet drug resistance was analyzed. At 3, 6 months, and 1 year after neurovascular intervention, adverse events were recorded through follow-up. The patients were divided into the occurrence group and the non-occurrence group according to whether adverse events occurred or not using the case-control study method. The Spearman correlation coefficient was used to analyze the correlation between adverse events and antiplatelet drug resistance after neurovascular intervention for cerebrovascular stenosis.Results:After 1 year of follow-up, among the 148 patients, 29 patients lost their follow-up, and 119 were included in the final analysis. Of the 119 patients, 41 patients had adverse events and 78 patients had no adverse events. In the occurrence group, the expression levels of platelet membrane glycoprotein P-selectin and platelet activating complex were (20.22 ± 6.33)% and (68.80 ± 11.52)%, respectively, before drug treatment, and they were (15.77 ± 4.12)% and (43.19 ± 5.90%)%, respectively, after drug treatment, all of which were significantly higher than those in the non-occurrence group [before drug treatment: (16.85 ± 3.24)%, (62.34 ± 10.77)%, after drug treatment: (8.31 ± 2.97)%, (35.85 ± 5.14)%] (before drug treatment: t = 3.20, 2.97, both P < 0.05; after drug treatment: t = 10.28, 6.74, both P < 0.05). The incidences of aspirin resistance and clopidogrel resistance in the occurrence group were 51.2% (21/41) and 43.9% (20/41), respectively, which were significantly higher than 26.9% (8/78) and 19.2% (9/78) in the non-occurrence group ( χ2 = 24.47, 20.23, both P < 0.001). Spearman correlation analysis showed that both aspirin resistance and clopidogrel resistance were moderately positively correlated with adverse events after neurovascular intervention ( r = 0.45, 0.41, both P < 0.05). Conclusion:Adverse events after neurovascular intervention are moderately positively correlated with resistance to the antiplatelet drugs aspirin and clopidogrel.

Evaluation of the Effect of Low-dose Aspirin on the Prevention of Preterm Delivery in Women with a History of Spontaneous Preterm Delivery / Avaliação do efeito da aspirina em baixa dose na prevenção do parto prematuro em mulheres com história de parto prematuro espontâneo

Abstract Objective Currently, uteroplacental vascular disorders are considered one of the main mechanisms of spontaneous preterm delivery (PTD). Low-dose aspirin is used to prevent pre-eclampsia, which has a similar mechanism; hence, the present study aimed to investigate the effect of low-dose aspirin on the prevention of PTD in women with a history of spontaneous PTD. Methods The present pilot randomized clinical trial was conducted on 54 pregnant women in the aspirin group (taking 80 mg daily until the 36th week and classic treatment) and 53 patients in the control group (only receiving classic treatment). Results Forty-three patients (40%) presented before 37 weeks due to symptoms of PTL. Preterm delivery (< 37 weeks) occurred in 28 patients (26%), and there was no significant difference between the aspirin and control groups (10 patients [19%] and 18 patients [34%], respectively; p = 0.069). The time of preterm delivery was early (< 34 weeks) in 6 patients (21%), and its cause was spontaneous labor in 23 patients (82%) which was not significantly different between the two groups (p > 0.05). Out of 40 patients with spontaneous labor, 25 patients (63%) had a PTD, which was significantly lower in the aspirin group than in the control group (9 patients [45%] versus 16 patients [80%], respectively; p = 0.022). Conclusion The findings of the present study demonstrated that despite the reduction in the incidence of PTD using low-dose aspirin, the reduction rate was not statistically significant. On the other hand, in patients with spontaneous labor prone to PTD, aspirin was effective in reducing the incidence of PTD.

Resumo Objetivo Atualmente, os distúrbios vasculares uteroplacentários são considerados um dos principais mecanismos de parto prematuro espontâneo (PTD). A aspirina em baixa dose é usada para prevenir a pré-eclâmpsia, que tem um mecanismo semelhante; portanto, o presente estudo teve como objetivo investigar o efeito da aspirina em baixa dosagem na prevenção de PTD em mulheres com história de PTD espontâneo. Métodos O presente ensaio clínico piloto randomizado foi realizado em 54 gestantes do grupo aspirina (tomando 80 mg diários até a 36ª semana e tratamento clássico) e 53 pacientes do grupo controle (somente tratamento clássico). Resultados Quarenta e três pacientes (40%) apresentaram-se antes de 37 semanas devido a sintomas de PTL. O parto prematuro (< 37 semanas) ocorreu em 28 pacientes (26%) e não houve diferença significativa entre os grupos aspirina e controle (10 pacientes [19%] e 18 pacientes [34%], respectivamente; p = 0,069). O tempo de parto prematuro foi precoce (< 34 semanas) em 6 pacientes (21%) e sua causa foi trabalho de parto espontâneo em 23 pacientes (82%) que não foi significativamente diferente entre os dois grupos (p > 0,05). Das 40 pacientes com trabalho de parto espontâneo, 25 pacientes (63%) tiveram PTD, que foi significativamente menor no grupo aspirina do que no grupo controle (9 pacientes [45%] versus 16 pacientes [80%], respectivamente; p = 0,022). Conclusão Os achados do presente estudo demonstraram que, apesar da redução na incidência de DPT com o uso de aspirina em baixa dosagem, a taxa de redução não foi estatisticamente significativa. Por outro lado, em pacientes com trabalho de parto espontâneo propensas a PTD, a aspirina foi eficaz na redução da incidência de PTD.

Indicación profiláctica de aspirina para prevención de preeclampsia y sus complicaciones en embarazos de alto y moderado riesgo / Prophylactic use of aspirin for the prevention of preeclampsia and its complications in high and moderate risk pregnancies

Resumen OBJETIVO: Sintetizar la evidencia disponible de los últimos 10 años respecto de la indicación de la aspirina para prevenir la preeclampsia y sus complicaciones en embarazos de alto y moderado riesgo. METODOLOGÍA: Revisión de cinco bases de datos [Pubmed/Medline, ProQuest, Lilacs, HINARI y Cochrane Central Register of Controlled Trials (CENTRAL)]. Se incluyeron ensayos clínicos aleatorizados, controlados, escritos en español o inglés publicados entre enero de 2010 y enero de 2020. Se emplearon los términos de vocabulario controlado DeCS y MeSH en las distintas interfases. En el caso de ProQuest se introdujeron, además, términos de vocabulario libre. Los detalles de la estrategia de búsqueda se visualizan en anexos. RESULTADOS: Se identificaron 410 estudios, de los que se seleccionaron 8 que reunieron los criterios de elegibilidad. En dos estudios se encontró un efecto reductor de la aspirina en la incidencia de preeclampsia en comparación con placebo; otros dos estudios encontraron el mismo efecto en la incidencia de preeclampsia con parto pretérmino. No se encontraron estudios con bajo riesgo de sesgo que hubieran reportado un efecto significativo de la aspirina en las complicaciones de preeclampsia, ni en preeclampsia con y sin criterios de severidad. CONCLUSIONES: La evidencia señala que la aspirina en bajas dosis, indicada antes de las 16 semanas de embarazo, reduce la incidencia de preeclampsia debido a su efecto reductor en el parto pretérmino. A pesar de lo encontrado, la información sigue siendo limitada; de ahí la necesidad de contar con una mayor cantidad de estudios con bajo riesgo de sesgo.

Abstract OBJECTIVE: To synthesize the available evidence of the last 10 years regarding the use of aspirin for the prevention of preeclampsia and its complications in high and moderate risk pregnancies. Methodology: Five electronic databases [Pubmed/Medline, ProQuest, Lilacs, HINARI, and Cochrane Central Register of Controlled Trials (CENTRAL)] were reviewed. Randomized controlled clinical trials in Spanish and English published between 01/01/2010 and 01/01/2020 were considered. The DeCS and MeSH controlled vocabulary terms were used in the different interfaces. In the case of ProQuest, free vocabulary terms were also introduced. The details of the search strategy are displayed in annexes. RESULTS: 410 studies were identified, of which 8 studies that met the eligibility criteria were selected. 2 studies found a reducing effect of aspirin on the incidence of preeclampsia compared to placebo and another 2 studies found the same effect on the incidence of preeclampsia with preterm delivery. No studies with low risk of bias were found that have reported a significant effect of aspirin on the complications of preeclampsia, nor on preeclampsia with and without criteria of severity. CONCLUSIONS: there is evidence indicating that low-dose aspirin before 16 weeks of gestation reduces the incidence of preeclampsia, this is due to the reducing impact it has on the incidence of preeclampsia with preterm delivery. Despite the results found, the information is still limited, and it is necessary to have a greater number of studies with low risk of bias.

Ácido acetilsalicílico versus inibidores dos receptores P2Y12 para prevenção secundária em pacientes tratados por meio de intervenção coronária percutânea / Aspirin versus P2Y12 inhibitors for secondary prevention after percutaneous coronary intervention

Na atualidade, as intervenções coronárias percutâneas com implante de um stent farmacológico constituem o principal método de revascularização miocárdica em centros hospitalares terciários, independentemente da forma clínica de apresentação da doença arterial coronária. É de conhecimento geral que, para sua efetivação, há necessidade do uso de um esquema antiplaquetário duplo, constituído pela associação do ácido acetilsalicílico e um inibidor dos receptores plaquetários P2Y12, que é o cerne da prevenção das tromboses após implantes das endopróteses, sendo também indicado para prevenir a ocorrência de eventos aterotrombóticos na evolução clínica tardia, qualquer que seja o modelo de stent utilizado. Após período variável de tempo, independentemente de fatores como forma clínica de apresentação da coronariopatia e do tipo de stent implantado, esse esquema é interrompido, e, na atualidade, as principais diretrizes preconizam a suspensão do inibidor dos receptores P2Y12 e a manutenção do ácido acetilsalicílico em longo prazo como uma das principais medidas farmacológicas de prevenção secundária da aterosclerose. No entanto, recentemente, em razão de sua maior potência antiplaquetária e provável menor potencial de causar hemorragias significantes, em especial no tubo digestivo, os inibidores P2Y12 têm sido considerados alternativa válida e atraente como antiplaquetário de utilização em longo prazo, alternativa ainda não referendada pelas diretrizes. Esta revisão discute os pormenores relacionados a essa importante decisão que deve ser tomada pelo cardiologista no momento da interrupção dos diferentes esquemas antitrombóticos inicialmente utilizados após uma intervenção coronária percutânea. Em princípio, a escassez de estudos clínicos conclusivos e normativos, em especial na população tratada por meio de uma intervenção percutânea, faz com que o ácido acetilsalicílico ainda se mantenha como o único antiagregante plaquetário com indicação classe I com a finalidade de prevenção secundária da aterosclerose.

Currently, percutaneous coronary intervention with a drug-eluting stent implantation is the main method of myocardial revascularization in tertiary care hospitals, regardless of the clinical presentation of coronary artery disease. It is well known that to be effective, it requires the use of a dual antiplatelet therapy, which is a combination of acetylsalicylic acid and a P2Y12 platelet receptor inhibitor, which plays a key role in preventing thromboses after endoprosthesis implantation and is also indicated to prevent atherothrombotic events in the late clinical course, regardless of the stent model used. After a variable period of time, depending on some factors, such as the clinical presentation of coronary artery disease and the type of stent implanted, this therapy is discontinued, and the main current guidelines recommend interrupting the P2Y12 receptor inhibitor and maintaining acetylsalicylic acid in the long term, as one of the main pharmacological measures for secondary prevention of atherosclerosis. However, recently, due to their greater antiplatelet potency and probable lower potential for significant bleeding, especially in the digestive tract, P2Y12 inhibitors have been considered a valid and attractive option as an antiplatelet agent for long-term use; but this alternative has not been endorsed by guidelines yet. This review discusses the details related to this important decision that must be made by cardiologists when discontinuing the different antithrombotic therapies initially used after percutaneous coronary intervention. In principle, the scarcity of conclusive and normative clinical studies, especially in the population treated by percutaneous intervention, means that acetylsalicylic acid is the only antiplatelet agent with class I indication for secondary prevention of atherosclerosis.

Aspirin and poetry: Did João Cabral de Melo Neto suffer from acetylsalicylic acid-overuse headache? / Aspirina e poesia: João Cabral de Melo Neto sofria de cefaleia por uso excessivo de ácido acetilsalicílico?

Introduction: João Cabral de Melo Neto is considered one of the most important Brazilian poets of all time. He suffered from severe headaches for the longest part of his life, being diagnosed with migraine. He took a significant amount of acetylsalicylic acid pills every day for many years. Objective: The objective of this narrative review includes identifying how headache and its treatment influenced João Cabral de Melo Neto's poetry as well as analyzing the correlation between Melo Neto's migraine diagnosis and his documented overuse of aspirin and investigating the possibility of an acetylsalicylic acid-overuse headache diagnosis. Methods: The authors thoroughly read biographical books and interviews about the life of João Cabral de Melo Neto. They systematically documented all references to headaches and aspirin. Melo Neto's clinical case documented in his biography and interviews were juxtaposed with The International Classification of Headache Disorders (ICHD-3) diagnostic criteria for acetylsalicylic acid-overuse headache diagnosis. Results: The word "aspirin" appears 8 times in 6 of Melo Neto's poems. He compares it to the sun, attributing to it the capacity to refocus a "blurred body" (his state during a headache). The poet reported that took one aspirin pill every hour every day, for several years. Conclusions: Headache and the use of acetylsalicylic acid influenced João Cabral de Melo Neto's poetry and life. He presented a risk behavior for developing medication overuse headache, specifically its subform: acetylsalicylic acid-overuse headache.

Introdução: João Cabral de Melo Neto é considerado um dos mais importantes poetas brasileiros de todos os tempos. Ele sofreu fortes dores de cabeça durante a maior parte de sua vida, sendo diagnosticado com enxaqueca. Ele tomou uma quantidade significativa de comprimidos de ácido acetilsalicílico todos os dias durante muitos anos. Objetivo: O objetivo desta revisão narrativa inclui identificar como a cefaleia e o seu tratamento influenciaram a poesia de João Cabral de Melo Neto, bem como analisar a correlação entre o diagnóstico de enxaqueca de Melo Neto e o seu documentado uso excessivo de aspirina e investigar a possibilidade de um diagnóstico de cefaleia por uso excessivo de ácido acetilsalicílico. Métodos: Os autores fazem leitura minuciosa de livros biográficos e entrevistas sobre a vida de João Cabral de Melo Neto. Eles documentaram sistematicamente todas as referências a dores de cabeça e aspirina. O caso clínico de Melo Neto documentado em sua biografia e entrevistas foi justaposto aos critérios diagnósticos da Classificação Internacional de Cefaleias (ICHD-3) para diagnóstico de cefaleia por uso excessivo de ácido acetilsalicílico. Resultados: A palavra "aspirina" aparece 8 vezes em 6 poemas de Melo Neto. Ele o compara ao sol, atribuindo-lhe a capacidade de reorientar um "corpo turvo" (seu estado durante uma dor de cabeça). O poeta relatou que tomou um comprimido de aspirina a cada hora, todos os dias, durante vários anos. Conclusões: A dor de cabeça e o uso de ácido acetilsalicílico influenciaram a poesia e a vida de João Cabral de Melo Neto. Apresentou comportamento de risco para desenvolver cefaleia por uso excessivo de medicamentos, especificamente sua subforma: cefaléia por uso excessivo de ácido acetilsalicílico.

Comparison of aspirin treatment strategies for primary prevention of cardiovascular diseases: A decision-analytic Markov modelling study / 北京大学学报(医学版)

OBJECTIVE@#To compare the expected population impact of benefit and risk of aspirin treatment strategies for the primary prevention of cardiovascular diseases recommended by different guidelines in the Chinese Electronic Health Records Research in Yinzhou (CHERRY) study.@*METHODS@#A decision-analytic Markov model was used to simulate and compare different strategies of aspirin treatment, including: Strategy ①: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk, recommended by the 2020 Chinese Guideline on the Primary Prevention of Cardiovascular Diseases; Strategy ②: Aspirin treatment for Chinese adults aged 40-59 years with a high 10-year cardiovascular risk, recommended by the 2022 United States Preventive Services Task Force Recommendation Statement on Aspirin Use to Prevent Cardiovascular Disease; Strategy ③: Aspirin treatment for Chinese adults aged 40-69 years with a high 10-year cardiovascular risk and blood pressure well-controlled (< 150/90 mmHg), recommended by the 2019 Guideline on the Assessment and Management of Cardio-vascular Risk in China. The high 10-year cardiovascular risk was defined as the 10-year predicted risk over 10% based on the 2019 World Health Organization non-laboratory model. The Markov model simulated different strategies for ten years (cycles) with parameters mainly from the CHERRY study or published literature. Quality-adjusted life year (QALY) and the number needed to treat (NNT) for each ischemic event (including myocardial infarction and ischemic stroke) were calculated to assess the effectiveness of the different strategies. The number needed to harm (NNH) for each bleeding event (including hemorrhagic stroke and gastrointestinal bleeding) was calculated to assess the safety. The NNT for each net benefit (i.e., the difference of the number of ischemic events could be prevented and the number of bleeding events would be added) was also calculated. One-way sensitivity analysis on the uncertainty of the incidence rate of cardiovascular diseases and probabilistic sensitivity analysis on the uncertainty of hazard ratios of interventions were conducted.@*RESULTS@#A total of 212 153 Chinese adults, were included in this study. The number of people who were recommended for aspirin treatment Strategies ①-③ was 34 235, 2 813, and 25 111, respectively. The Strategy ③ could gain the most QALY of 403 [95% uncertainty interval (UI): 222-511] years. Compared with Strategy ①, Strategy ③ had similar efficiency but better safety, with the extra NNT of 4 (95%UI: 3-4) and NNH of 39 (95%UI: 19-132). The NNT per net benefit was 131 (95%UI: 102-239) for Strategy ①, 256 (95%UI: 181-737) for Strategy ②, and 132 (95%UI: 104-232) for Strategy ③, making Strategy ③ the most favorable option with a better QALY and safety, along with similar efficiency in terms of net benefit. The results were consistent in the sensitivity analyses.@*CONCLUSION@#The aspirin treatment strategies recommended by the updated guidelines on the primary prevention of cardiovascular diseases showed a net benefit for high-risk Chinese adults from developed areas. However, to balance effectiveness and safety, aspirin is suggested to be used for primary prevention of cardiovascular diseases with consideration for blood pressure control, resulting in better intervention efficiency.